RESUMEN
Here we investigated the nature and functional consequences of mutations in the HIV-1 tat gene within an epidemiologically-linked AIDS transmission cohort consisting of a non-progressing donor (A) and two normal progressing recipients (B and C). Multiple nonsynonymous mutations in the tat first exon were observed across time in all individuals. Some mutations demonstrated striking host specificity despite the cohort being infected with a common virus. Phylogenetic segregation of the tat clones at the time of progression to AIDS was also observed especially in recipient C. Tat clones supporting high levels of transactivation were present at all time points in all individuals, although a number of clones defective for transactivation were observed for recipient C in later time points. Here we show that the tat quasispecies in a linked transmission cohort diversify and evolve independently between hosts following transmission. It supports the belief that quasispecies variation in HIV-1 is a mechanism for selection towards defining a fitter gene variant that is capable of resisting the human immune system.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/transmisión , Síndrome de Inmunodeficiencia Adquirida/virología , Productos del Gen tat/genética , VIH-1/genética , Síndrome de Inmunodeficiencia Adquirida/inmunología , Estudios de Cohortes , Exones , Productos del Gen tat/química , VIH-1/clasificación , Células HeLa , Humanos , Mutación , Reacción a la TransfusiónRESUMEN
Epidemiologically-linked HIV-1 transmission cohorts serve as excellent models to study HIV disease progression. The actual relationship between viral variability and HIV disease outcome can be extrapolated only through such rare epidemiologically linked HIV-1-infected cohorts. We present here a cohort of three patients with the source termed donor A (a nonprogressor) and two recipients B and C. Both recipients acquired HIV through blood transfusion from donor A and have progressed to AIDS. By analyzing 15 near full-length HIV- 1 genomes (8.7 kb each genome) from longitudinally collected peripheral blood cell samples (four time points for patient A, four for patient B, and seven from patient C), we were able to demonstrate transmission of HIV from donor A and epidemiologic linkage among members A, B, and C after 10 years of HIV infection. These analyses are novel in demonstrating that HIV-1-infected nonprogressing individuals bear the potential to transmit HIV-1 variants and that HIV variants, which led to a benign disease in a nonprogressor donor, were able to cause disease in other individuals. Overall, these studies highlight the utility of full genome sequencing in establishing epidemiologic linkage in a chronically infected HIV cohort after 10 years of initial infection.